Singer M S, Oliveira L, Vriend G, Shepherd G M
Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Recept Channels. 1995;3(2):89-95.
A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.
人们认为，一类G蛋白偶联受体介导了气味分子的识别。为了确定潜在的配体结合残基，我们对大鼠的受体序列进行了相关突变分析。该方法可识别出残基保持保守或串联突变的序列位置对，从而表明其结构或功能上的重要性。该分析支持了分子建模研究，提示了一些与配体结合功能一致位置上的残基。其中两个位置以组氨酸残基为主，可能在配体结合中起重要作用，并可能赋予哺乳动物气味受体广泛的特异性。在一些已确定的位置上存在正向（超显性）选择，为其在配体结合中的作用提供了额外证据。还观察到了高阶相关残基组。每个组可能与单个配体决定簇相互作用，这些组的组合可能为受体多样性提供多维机制。
